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Vasoactive intestinal peptide receptors in pancreas and liver. Structure-function relationship
J Christophe1, M Svoboda, M Waelbroeck
1Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Annals of the New York Academy of Sciences
|January 1, 1988
Summary
This study differentiates VIP-preferring receptors in rat pancreas using VIP agonists, revealing distinct characteristics from liver VIP receptors and identifying specific protein sizes in pancreatic membranes.
Area of Science:
- Biochemistry
- Molecular Pharmacology
- Gastroenterology
Background:
- Vasoactive intestinal peptide (VIP) receptors mediate diverse physiological functions.
- Distinguishing between VIP receptor subtypes is crucial for understanding VIP signaling.
- Rat pancreatic and hepatic VIP receptors exhibit differential properties.
Purpose of the Study:
- To characterize VIP receptors in rat pancreas and liver.
- To differentiate between VIP-preferring and secretin-preferring receptors.
- To investigate the molecular properties and signaling coupling of VIP receptors.
Main Methods:
- Radioligand binding assays using VIP analogues and helodermin.
- Adenylate cyclase activation assays.
- [125I]VIP cross-linking and molecular weight determination.
Main Results:
- (D-Phe4)PHI acts as a selective VIP agonist for pancreatic VIP-preferring receptors.
- Pancreatic VIP receptors require disulfide bridges and show poor adenylate cyclase coupling compared to hepatic receptors.
- High-affinity hepatic VIP receptors are well coupled to adenylate cyclase, unlike low-affinity ones.
- Cross-linking studies identified distinct peptide sizes (66/35 kDa in pancreas, 56 kDa in liver) and a larger complex (130-180 kDa) in intact pancreatic acini.
Conclusions:
- VIP-preferring receptors in the rat pancreas have unique biochemical and functional properties.
- Hepatic VIP receptors display differential affinity and coupling efficiency.
- Identified protein species suggest distinct receptor structures and potential precursor-product relationships.